2 CNS Tumors IncidenceThe annual incidence of tumors of the CNS ranges from:10 to 17 per 100,000 persons for intracranial tumors1 to 2 per 100,000 persons for intraspinal tumorsAbout half to three-quarters are primary tumors, and the rest are metastatic
3 CNS Tumors and childhood Tumors of the CNS are a large proportion of cancers of childhood, accounting for as many of 20% of all tumorsCNS tumors in childhood differ from those in adults both in histologic subtype and locationIn childhood, tumors are likely to arise in the posterior fossa, while in adults they are mostly supratentorial
4 CNS Tumors General characteristics The anatomic site of the neoplasm can have lethal consequences irrespective of histological classification (i.e. benign tumors can be fatal in certain locations) examples on such locations?These tumors do not have detectable premalignant or in situ stages comparable to those of carcinomasThe pattern of spread of primary CNS neoplasms differs from that of other tumors:rarely metastasize outside the CNSthe subarachnoid space does provide a pathway for spread What are the layers that surround subarachnoid space?
5 CNS Tumors General characteristics Even low-grade lesions may infiltrate large regions of the brain, leading to serious clinical deficits, nonresectability, and poor prognosis
6 CNS Tumors General manifestations Seizures, headaches, vague symptomsFocal neurologic deficits related to the anatomic site of involvementRate of growth may correlate with history
7 CNS tumors Classification May arise from:cells of the coverings (meningiomas)cells intrinsic to the brain (gliomas, neuronal tumors, choroid plexus tumors)other cell populations within the skull (primary CNS lymphoma, germ-cell tumors)they may spread from elsewhere in the body (metastases)
9 CNS Tumors Astrocytomas Fibrillary:4th to 6th decadeCommonly cerebral hemisphereVariable grades:Diffuse astrocytoma (Grade II )Anaplstic astrocytoma (Grade III )Glioblastoma ( Grade IV )Pilocytic ( Grade I )Children and young adultsCommonly cerebellumRelatively benign
10 CNS Tumors Fibrillary Astrocytoma Well differentiated “diffuse astrocytoma” (WHO grade II) :Static or progress slowly (mean survival of more than 5 years)Moderate cellularityVariable nuclear pleomorphismLess differentiated (higher-grade) :Anaplstiac astrocytoma (WHO grade III)More cellularGreater nuclear pelomrophismMitosisGlioblastoma (WHO grade IV) :With treatment, mean survival of 8-10 monthsAll the features of anaplastic astrocytoma, plus:Necrosis and/or vascular or endothelial cell proliferation
11 Note that diffuse astrocytoma are poorly demarcated
13 CNS Tumors Astrocytoma Mutations that alter the enzymatic activity of two isoforms of the metabolic enzyme isocitrate dehydrogenase (IDH1 and IDH2) are common in lower-grade astrocytomas
14 CNS Tumors Glioblastoma Secondary glioblastomas share p53 mutations that characterized low-grade gliomasWhile primary glioblastomas are characterized by amplification of the epidermal growth factor receptor (EGFR ) gene
15 CNS Tumors Pilocytic Astrocytoma Often cystic, with a mural noduleWell circumscribed"hairlike“=pilocytic processes that are GFAP positiveRosenthal fibers & hyaline granular bodies are often presentNecrosis and mitoses are typicallyabsent
17 CNS Tumors Oligodendroglioma The most common genetic findings are loss of heterozygosity for chromosomes 1p and 19qFourth and fifth decadesCerebral hemispheres, with a predilection for white matterBetter prognosis than do patients with astrocytomas (5 to 10 years with Rx)Anaplastic form prognosis is worse
18 In oligodendroglioma tumor cells have round nuclei, often with a cytoplasmic halo Blood vessels in the background are thin and can form an interlacing patternWhat additional features are needed for anaplastic oligodendroglioma?
20 CNS Tumors EpendymomaMost often arise next to the ependyma-lined ventricular system, including the central canal of the spinal cordOccurs in the first two decades of life, they typically occur near the fourth ventricleIn adults, the spinal cord is their most common location
21 CNS Tumors EpendymomaTumor cells may form round or elongated structures (rosettes, canals) what is a rosette?perivascular pseudo-rosettesAnaplastic ependymomas show increased cell density, high mitotic rates, necrosis and less evident ependymal differentiation
23 CNS Tumors Meningioma Predominantly benign tumors of adults Origin: meningothelial cell of the arachnoid
24 CNS Tumors Meningioma Well demarcated Attached to the dura with compression of underlying brainWhorled pattern of cell growth and psammoma bodies
25 CNS Tumors Meningioma Main subtypes: Also note: Syncytial Fibroblastic TransitionalAlso note:Atypical meningiomasAnaplastic (malignant) meningiomas
26 CNS Tumors MeningiomaAlthough most meningiomas are easily separable from underlying brain, some tumors infiltrate the brain.The presence of brain invasion is associated with increased risk of recurrence.
28 CNS Tumors Medulloblastoma Children and exclusively in the cerebellumNeuronal and glial markers may be expressed, but the tumor is often largely undifferentiatedThe tumor is highly malignant, and the prognosis for untreated patients is dismal; however, it is exquisitely radiosensitiveWith total excision and radiation, the 5-year survival rate may be as high as 75%
32 Nervous system Tumors Schwannoma BenignIn the CNS, they are often encountered within the cranial vault in the cerebellopontine angle, where they are attached to the vestibular branch of the eighth nerve (tinnitus and hearing loss)Bilateral = NF2
33 Nervous system Tumors Schwannoma Sporadic schwannomas are associated with mutations in the NF2 geneBilateral acoustic schwannoma is associated with NF2Attached to the nerve but can be separated from it
34 Nervous system Tumors Schwannoma Cellular Antoni A pattern and less cellular Antoni Bnuclear-free zones of processes that lie between the regions of nuclear palisading are termed Verocay bodies
36 Nervous system Tumors Neurofibroma Examples: (cutaneous neurofibroma) or in peripheral nerve (solitary neurofibroma)These arise sporadically or in association with type 1 neurofibromatosis, rarely malignantplexiform neurofibroma, mostly arising in individuals with NF1, potential malignancyNeurofibromas cannot be separated from nerve trunk (in comparison to shcwannoma)
38 Nervous system Tumors Metastatic tumours About half to three-quarters of brain tumors are primary tumors, and the rest are metastaticLung, breast, skin (melanoma), kidney, and gastrointestinal tract are the commonestSharply demarcated masses with edema.
40 Homework! FAMILIAL TUMOR SYNDROMES - Describe the inheritance pattern and the main features of:Type 1 NeurofibromatosisType 2 NeurofibromatosisWhich one of these two syndromes, has a propensity for the neurofibromas to undergo malignant transformation at a higher rate than that observed for comparable tumors in the general population?Tip: use the recommended textbook and the internet.